DNF seminar
Abstract:
My lab investigates motor and cognitive circuits and how they are reorganised in Parkinson’s disease (PD). My presentation will be divided into two parts.
In the first part, I will report how we have identified the Zona Incerta (ZI) as a key component in encoding and processing anxiety. Using a biochemical approach and in-vivo calcium imaging, we showed that the ZI senses anxiety when mice experience open and elevated environments. Complementarily, diazepam infusion directly into the ZI reduces anxiety. Considering the cellular heterogeneity of the ZI, we next optogenetically assessed the differential contribution of somatostatin (SOM-), calretinin (CR-) and excitatory (Vglut2-) neuronal subpopulations in anxiety-related behaviors. While the photoactivation of SOM- expressing ZI neurons enhances anxiety, the photoactivation of CR- positive ZI neurons reduces anxiety and promotes rearing. And the activation of Vglut2- expressing ZI neurons triggers escape-like jumps. Together, these data reveal that ZI subpopulations encode and modulate different component of anxiety.
In the second part, I will present you our latest data set related to our pre-clinical research angle. Parkinson’s disease remains a non-curable neurodegenerative disorder which has an enormous negative impact on the patients but also our health care system, society, and economy. With the aim to respond this unmet need, we teamed up with with M. Fussenegger (ETHZ-DBSSE). We have generated a high throughput screening method that reveals high efficacy compounds with potential neuroprotective pharmaco-therapeutical application in Parkinson’s disease. Combining in vitro electrophysiology, histology and in vivo calcium imaging in locomoting mouse model of PD, we report that one of our hit compound preserves 90% of dopamine neuronal integrity. It also preserves the striatal neuronal dynamics as well as locomotion performance. This compound hence exhibits neuroprotective effects and may be further developed as pharmacotherapy in PD.